The cerebral protective effects of 4-week treatment with candesartan (0.3, 1, 3 mg/kg/day) and ramipril (0.5, 1.5, 5 mg/kg/day) were examined in spontaneous hypertensive rats 24 h after middle cerebral artery occlusion. We found that both candesartan and ramipril could reduce the infarct volume and neurological deficit scores compared with control. Importantly, the neuroprotective effects of candesartan (1 mg/kg/day) were abolished by PD123319 (an AT2 receptor antagonist, 10 mg/kg/day). AT1 receptor gene expression was downregulated while AT2 receptor gene expression was upregulated by candesartan. It is concluded that candesartan appears to provide beneficial effects against stroke in spontaneous hypertensive rats in three ways: AT1 receptor antagonism, downregulation of AT1 receptor expression and upregulation of AT2 receptor expression.